Blocking of neuronal functioning or denervation, either pharmacological or surgical, often results in up regulation in the postsynaptic target tissue (increased receptor binding of the agonist compounds related to the dysfunctioned nerves). A consequence of up regulation is supersensitivity (oversized physiological or behavioral responses by the agonist stimulation). There are neurons where two neuroceretory systems coexist within the same terminal. Vasoactive intestinal peptide (VIP) and acetylcholine (ACh) coexist in postganglionic neurons which innervate the salivary glands and cholecystokinin (CCK) coexists with dopamine (DA) in the mesolimbic neurons. It has been shown that atropine blocking of ACh results in up regulation and supersensitivity in VIP receptor system. DA blocking is known to result in increased binding of CCK-8 in selected areas of the brain. We showed recently that DA system dysfunctioning by 6-hydroxydopamine (6-OHDA) made the animal sensitive to the effect of CCK-8 to increase general activity. It is proposed that this effect of increased sensitivity to CCK-8 following 6-OHDA treatment be critically examined with (a) the behaviors (open field) which are more sensitive to CCK-8, (b)\animals brain-lesioned in two different areas (nucleus accumbens septi and corpus striatum), and (c) various CCK analogs (CCK-8, nonsulfated CCK-8 and CCK-4) and (d) a CCK-8 blocking compound (proglumide). EXP. 1 examines the site specificity of apomorphine supersensitivity by having accumbens-lesioned and striatum-lesioned animals compared against their respective sham-lesioned animals. It is expected that supersensitivity occurs only to accumbens-lesioned animals. EXP. 2 examines the effectiveness of lesioning by amphetamine. It is expected that amphetamine loses its effect in accumbens-lesioned animals. EXP. 3 examines whether accumbens-lesioned supersensitivity occurs to CCK analogs. It is expected that only CCK-8 will produce supersensitivity. EXP. 4 examines the effect of proglumide on CCK supersensitivity. We expect the CCK effect to be blocked equally in sensitized or non-sensitized animals. EXP. 5 examines the effect of chronic DA blocking by haloperidol on development of CCK supersensitivity. It is expected that this pharmacological DA blocking will result in CCK supersensitivity. In the long run it is hoped that development of CCK supersensitivity may explain some therapeutic or side effects of DA blocking compound or some symptoms involving DA dysfunctioning.